The proposed research program will study the effects of alcohol on pyridoxine and folate metabolism as it effects normal human tissues. A number of new techniques have been developed to study the internal kinetics of folic acid and pyridoxine in man. Pathways of uptake, conversion to active vitamins, storage and delivery can now be characterized using isotope-labelled materials and sophisticated techniques of column chromatography and high voltage electrophoresis. Normal metabolic pathways of these substances have now been characterized. This permits detailed studies of the effect of alcohol on the generation of the active forms of the vitamins. In the case of folic acid, primary attention will be directed to the possible effect of alcohol on interfering with the release of storage forms of folic acids tissues requiring the vitamin for DNA metabolism. For pyridoxine, studies will be aimed at characterizing the effect of alcohol on the kinase and oxidase enzymes required for conversion for pyridoxal-5-phosphate. In addition, treatment protocols will be carried out to look for possible benefits of using pyridoxal-5-phosphate to treat both alcoholic sideroblastic anemia and acquired sideroblastic anemias of unknown etiology.